YOD1 Data Analysis

HGNC Gene Name
YOD1 deubiquitinase
HGNC Gene Symbol
YOD1
Identifiers
hgnc:25035 NCBIGene:55432 uniprot:Q5VVQ6
Orthologs
mgi:2442596 rgd:1359726
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for YOD1
Number of Papers
48 retrieved on 2022-05-22

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol Name DepMap Correlation Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with YOD1using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier GO Name GO Type p-value p-value (adj.) q-value

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out YOD1 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
APBB1IP amyloid beta precursor protein binding family B member 1 interacting protein 7.85e-01 1.35e-07 3.81e-04
ANKRD1 ankyrin repeat domain 1 4.09e-01 4.62e-07 6.51e-04
SNRNP200 small nuclear ribonucleoprotein U5 subunit 200 6.96e-01 9.56e-07 8.97e-04
TAGLN2 transgelin 2 -4.33e-01 3.08e-06 2.17e-03
RPL39 ribosomal protein L39 3.94e-01 5.99e-06 3.37e-03
GNG5 G protein subunit gamma 5 -3.89e-01 1.98e-05 8.96e-03
RPSA ribosomal protein SA 7.62e-01 2.23e-05 8.96e-03
MIER1 MIER1 transcriptional regulator 5.54e-01 2.84e-05 1.00e-02
CLINT1 clathrin interactor 1 6.41e-01 3.30e-05 1.03e-02
SAA2 serum amyloid A2 -7.94e-01 5.10e-05 1.44e-02
RPL7L1 ribosomal protein L7 like 1 2.64e-01 6.04e-05 1.55e-02
ANLN anillin actin binding protein 6.04e-01 1.27e-04 2.99e-02
SAA1 serum amyloid A1 -6.56e-01 1.47e-04 3.17e-02
AGTRAP angiotensin II receptor associated protein -7.12e-01 2.67e-04 4.58e-02
CD82 CD82 molecule -5.31e-01 3.21e-04 4.58e-02
HNRNPA3 heterogeneous nuclear ribonucleoprotein A3 3.89e-01 3.26e-04 4.58e-02
HSPA9 heat shock protein family A (Hsp70) member 9 3.80e-01 2.82e-04 4.58e-02
NOP14 NOP14 nucleolar protein 6.32e-01 2.68e-04 4.58e-02
TIMP1 TIMP metallopeptidase inhibitor 1 -3.22e-01 2.96e-04 4.58e-02
TMOD3 tropomodulin 3 6.17e-01 3.24e-04 4.58e-02
PRC1 protein regulator of cytokinesis 1 4.48e-01 3.63e-04 4.87e-02

Gene Set Enrichment Analysis

The GSEA method was applied for all genes whose knockout resulted in at least 20 significantly differentially expressed genes.

ID Name p-value p-value (adj.) log2 Error ES NES
msig:M5893 HALLMARK_MITOTIC_SPINDLE 3.75e-10 9.09e-07 8.14e-01 6.49e-01 2.42e+00
go:0042393 histone binding 5.39e-08 5.32e-05 7.20e-01 6.50e-01 2.32e+00
go:0033044 regulation of chromosome organization 6.58e-08 5.32e-05 7.05e-01 5.43e-01 2.20e+00
go:0045787 positive regulation of cell cycle 2.26e-06 1.09e-03 6.27e-01 4.93e-01 2.02e+00
go:0051276 chromosome organization 2.86e-06 1.09e-03 6.27e-01 3.68e-01 1.73e+00
go:0045944 positive regulation of transcription by RNA polymerase II 3.15e-06 1.09e-03 6.27e-01 4.19e-01 1.86e+00
go:0033043 regulation of organelle organization 9.07e-06 2.75e-03 5.93e-01 3.47e-01 1.65e+00
go:2001251 negative regulation of chromosome organization 1.17e-05 3.16e-03 5.93e-01 6.13e-01 2.14e+00
go:0007010 cytoskeleton organization 1.94e-05 4.52e-03 5.76e-01 3.62e-01 1.69e+00
go:0050728 negative regulation of inflammatory response 2.05e-05 4.52e-03 5.76e-01 -7.24e-01 -2.18e+00
go:0006091 generation of precursor metabolites and energy 2.66e-05 4.97e-03 5.76e-01 -3.55e-01 -1.73e+00
go:0008144 drug binding 2.51e-05 4.97e-03 5.76e-01 3.49e-01 1.65e+00
go:0031252 cell leading edge 3.10e-05 5.01e-03 5.57e-01 5.07e-01 1.98e+00
go:0051726 regulation of cell cycle 2.97e-05 5.01e-03 5.76e-01 3.48e-01 1.64e+00
go:0045931 positive regulation of mitotic cell cycle 3.52e-05 5.18e-03 5.57e-01 5.61e-01 2.00e+00
go:0003700 DNA-binding transcription factor activity 3.63e-05 5.18e-03 5.57e-01 4.14e-01 1.79e+00
go:0030554 adenyl nucleotide binding 3.95e-05 5.32e-03 5.57e-01 3.48e-01 1.64e+00
go:0005819 spindle 4.57e-05 5.83e-03 5.57e-01 4.53e-01 1.88e+00
go:0007049 cell cycle 5.18e-05 6.29e-03 5.57e-01 3.06e-01 1.52e+00
go:0140053 mitochondrial gene expression 6.13e-05 6.76e-03 5.38e-01 -4.58e-01 -1.92e+00
go:0005694 chromosome 5.96e-05 6.76e-03 5.57e-01 3.45e-01 1.62e+00
go:0006325 chromatin organization 7.30e-05 7.69e-03 5.38e-01 3.92e-01 1.74e+00
go:0009891 positive regulation of biosynthetic process 7.92e-05 8.00e-03 5.38e-01 3.25e-01 1.57e+00
msig:M5935 HALLMARK_FATTY_ACID_METABOLISM 8.49e-05 8.24e-03 5.38e-01 -4.98e-01 -1.96e+00
go:0032553 ribonucleotide binding 1.03e-04 9.65e-03 5.38e-01 3.27e-01 1.58e+00
go:0051052 regulation of DNA metabolic process 1.26e-04 1.09e-02 5.19e-01 4.84e-01 1.88e+00
go:0090068 positive regulation of cell cycle process 1.26e-04 1.09e-02 5.19e-01 4.80e-01 1.88e+00
msig:M5942 HALLMARK_UV_RESPONSE_DN 1.31e-04 1.10e-02 5.19e-01 6.26e-01 2.00e+00
go:0044430 1.49e-04 1.16e-02 5.19e-01 3.22e-01 1.54e+00
go:0000922 spindle pole 1.48e-04 1.16e-02 5.19e-01 5.29e-01 1.93e+00
go:0008092 cytoskeletal protein binding 1.77e-04 1.34e-02 5.19e-01 3.69e-01 1.68e+00
reactome:R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT) 2.22e-04 1.54e-02 5.19e-01 -7.30e-01 -2.08e+00
go:0003723 RNA binding 2.31e-04 1.55e-02 5.19e-01 2.74e-01 1.40e+00
go:0006302 double-strand break repair 2.56e-04 1.68e-02 4.98e-01 5.51e-01 1.95e+00
go:0000278 mitotic cell cycle 2.73e-04 1.70e-02 4.98e-01 3.20e-01 1.51e+00
go:0004386 helicase activity 2.68e-04 1.70e-02 4.98e-01 5.53e-01 1.93e+00
go:0007051 spindle organization 2.81e-04 1.70e-02 4.98e-01 5.03e-01 1.88e+00
go:0010639 negative regulation of organelle organization 3.54e-04 1.94e-02 4.98e-01 4.22e-01 1.74e+00
go:0098813 nuclear chromosome segregation 3.60e-04 1.94e-02 4.98e-01 4.70e-01 1.84e+00
go:0010628 positive regulation of gene expression 3.60e-04 1.94e-02 4.98e-01 3.12e-01 1.51e+00
msig:M5901 HALLMARK_G2M_CHECKPOINT 3.56e-04 1.94e-02 4.98e-01 4.27e-01 1.75e+00
go:0003779 actin binding 3.58e-04 1.94e-02 4.98e-01 4.24e-01 1.72e+00
go:0007163 establishment or maintenance of cell polarity 3.71e-04 1.96e-02 4.98e-01 5.43e-01 1.92e+00
msig:M14314 KEGG_PURINE_METABOLISM 3.84e-04 1.98e-02 4.98e-01 -5.28e-01 -1.98e+00
go:0044429 4.56e-04 2.30e-02 4.98e-01 -2.81e-01 -1.46e+00
go:2001252 positive regulation of chromosome organization 4.76e-04 2.36e-02 4.98e-01 5.10e-01 1.86e+00
go:0000226 microtubule cytoskeleton organization 5.21e-04 2.53e-02 4.77e-01 3.98e-01 1.71e+00
go:0007017 microtubule-based process 5.70e-04 2.66e-02 4.77e-01 3.69e-01 1.64e+00
reactome:R-HSA-977225 Amyloid fiber formation 5.69e-04 2.66e-02 4.77e-01 -6.51e-01 -1.96e+00
go:0005874 microtubule 6.01e-04 2.75e-02 4.77e-01 4.17e-01 1.70e+00
go:0010564 regulation of cell cycle process 6.20e-04 2.78e-02 4.77e-01 3.38e-01 1.57e+00
go:0005770 late endosome 6.73e-04 2.97e-02 4.77e-01 -4.78e-01 -1.86e+00
go:0000819 sister chromatid segregation 7.12e-04 3.08e-02 4.77e-01 4.81e-01 1.82e+00
msig:M5936 HALLMARK_OXIDATIVE_PHOSPHORYLATION 7.49e-04 3.16e-02 4.77e-01 -3.55e-01 -1.63e+00
go:0050839 cell adhesion molecule binding 7.58e-04 3.16e-02 4.77e-01 3.60e-01 1.60e+00
go:0051983 regulation of chromosome segregation 7.69e-04 3.16e-02 4.77e-01 5.54e-01 1.87e+00
go:0099080 supramolecular complex 8.18e-04 3.31e-02 4.77e-01 3.60e-01 1.60e+00
go:0006310 DNA recombination 9.04e-04 3.59e-02 4.77e-01 4.68e-01 1.75e+00
go:0000726 non-recombinational repair 9.33e-04 3.64e-02 4.77e-01 6.41e-01 1.86e+00
go:0000018 regulation of DNA recombination 9.46e-04 3.64e-02 4.77e-01 6.84e-01 1.92e+00
go:0051783 regulation of nuclear division 9.84e-04 3.73e-02 4.55e-01 4.74e-01 1.80e+00
go:0043565 sequence-specific DNA binding 1.03e-03 3.85e-02 4.55e-01 3.87e-01 1.67e+00
go:0003682 chromatin binding 1.07e-03 3.93e-02 4.55e-01 3.99e-01 1.68e+00
go:0044463 1.09e-03 3.93e-02 4.55e-01 3.48e-01 1.58e+00
go:0016071 mRNA metabolic process 1.11e-03 3.94e-02 4.55e-01 3.27e-01 1.52e+00
go:0000228 nuclear chromosome 1.19e-03 4.19e-02 4.55e-01 3.65e-01 1.58e+00
go:0032838 plasma membrane bounded cell projection cytoplasm 1.22e-03 4.22e-02 4.55e-01 5.68e-01 1.84e+00
go:0014070 response to organic cyclic compound 1.27e-03 4.26e-02 4.55e-01 3.58e-01 1.57e+00
go:0051129 negative regulation of cellular component organization 1.28e-03 4.26e-02 4.55e-01 3.54e-01 1.55e+00
go:0015630 microtubule cytoskeleton 1.32e-03 4.29e-02 4.55e-01 3.22e-01 1.51e+00
reactome:R-HSA-71387 Metabolism of carbohydrates 1.33e-03 4.29e-02 4.55e-01 -4.32e-01 -1.75e+00
reactome:R-HSA-72306 tRNA processing 1.35e-03 4.31e-02 4.55e-01 -5.44e-01 -1.91e+00
go:0032543 mitochondrial translation 1.38e-03 4.32e-02 4.55e-01 -4.16e-01 -1.72e+00
reactome:R-HSA-397014 Muscle contraction 1.40e-03 4.32e-02 4.55e-01 5.76e-01 1.84e+00
go:0005740 mitochondrial envelope 1.47e-03 4.46e-02 4.55e-01 -2.69e-01 -1.38e+00
go:0016887 ATPase activity 1.66e-03 4.62e-02 4.55e-01 3.88e-01 1.64e+00
go:0140014 mitotic nuclear division 1.62e-03 4.62e-02 4.55e-01 3.98e-01 1.61e+00
go:0030424 axon 1.60e-03 4.62e-02 4.55e-01 4.11e-01 1.65e+00
go:0071407 cellular response to organic cyclic compound 1.65e-03 4.62e-02 4.55e-01 3.92e-01 1.61e+00
go:0030175 filopodium 1.66e-03 4.62e-02 4.55e-01 6.65e-01 1.87e+00
go:0019068 virion assembly 1.62e-03 4.62e-02 4.55e-01 -6.37e-01 -1.88e+00
msig:M5898 HALLMARK_DNA_REPAIR 1.77e-03 4.88e-02 4.55e-01 -4.29e-01 -1.75e+00
go:0071887 leukocyte apoptotic process 1.86e-03 5.01e-02 4.55e-01 -6.15e-01 -1.93e+00
go:0007346 regulation of mitotic cell cycle 1.88e-03 5.01e-02 4.55e-01 3.34e-01 1.53e+00
go:0072686 mitotic spindle 1.93e-03 5.10e-02 4.55e-01 5.16e-01 1.78e+00
go:0007059 chromosome segregation 2.15e-03 5.61e-02 4.32e-01 3.94e-01 1.60e+00
reactome:R-HSA-5368287 Mitochondrial translation 2.26e-03 5.80e-02 4.32e-01 -4.23e-01 -1.71e+00
go:0008017 microtubule binding 2.27e-03 5.80e-02 4.32e-01 4.88e-01 1.76e+00
go:0000785 chromatin 2.37e-03 5.87e-02 4.32e-01 3.75e-01 1.59e+00
go:0140030 modification-dependent protein binding 2.34e-03 5.87e-02 4.32e-01 5.88e-01 1.83e+00
go:0045296 cadherin binding 2.45e-03 5.87e-02 4.32e-01 3.60e-01 1.57e+00
go:0000070 mitotic sister chromatid segregation 2.50e-03 5.87e-02 4.32e-01 4.67e-01 1.73e+00
go:0002285 lymphocyte activation involved in immune response 2.51e-03 5.87e-02 4.32e-01 5.99e-01 1.76e+00
go:0003690 double-stranded DNA binding 2.52e-03 5.87e-02 4.32e-01 3.79e-01 1.61e+00
go:0050000 chromosome localization 2.54e-03 5.87e-02 4.32e-01 5.95e-01 1.83e+00
go:0022402 cell cycle process 2.44e-03 5.87e-02 4.32e-01 2.91e-01 1.41e+00
go:0005126 cytokine receptor binding 2.39e-03 5.87e-02 4.32e-01 -5.40e-01 -1.85e+00
go:0051301 cell division 2.59e-03 5.93e-02 4.32e-01 3.38e-01 1.51e+00
go:0016614 oxidoreductase activity, acting on CH-OH group of donors 2.78e-03 6.31e-02 4.32e-01 -5.53e-01 -1.87e+00
go:0045935 positive regulation of nucleobase-containing compound metabolic process 2.84e-03 6.39e-02 4.32e-01 4.33e-01 1.66e+00
go:0016817 hydrolase activity, acting on acid anhydrides 2.91e-03 6.47e-02 4.32e-01 3.11e-01 1.44e+00
go:0032204 regulation of telomere maintenance 3.14e-03 6.57e-02 4.32e-01 5.74e-01 1.78e+00
go:0070126 mitochondrial translational termination 3.10e-03 6.57e-02 4.32e-01 -4.21e-01 -1.69e+00
go:0030010 establishment of cell polarity 3.14e-03 6.57e-02 4.32e-01 5.94e-01 1.78e+00
go:0042641 actomyosin 3.08e-03 6.57e-02 4.32e-01 6.56e-01 1.84e+00
go:0048285 organelle fission 3.13e-03 6.57e-02 4.32e-01 3.73e-01 1.58e+00
go:2000106 regulation of leukocyte apoptotic process 3.02e-03 6.57e-02 4.32e-01 -6.21e-01 -1.84e+00
go:0008380 RNA splicing 3.01e-03 6.57e-02 4.32e-01 3.27e-01 1.50e+00
go:0010638 positive regulation of organelle organization 3.18e-03 6.59e-02 4.32e-01 3.36e-01 1.49e+00
reactome:R-HSA-5578749 Transcriptional regulation by small RNAs 3.38e-03 6.85e-02 4.32e-01 -5.29e-01 -1.81e+00
go:1902275 regulation of chromatin organization 3.38e-03 6.85e-02 4.32e-01 4.94e-01 1.72e+00
reactome:R-HSA-211000 Gene Silencing by RNA 3.39e-03 6.85e-02 4.32e-01 -5.20e-01 -1.83e+00
go:0000910 cytokinesis 3.44e-03 6.89e-02 4.32e-01 4.95e-01 1.77e+00
go:0015631 tubulin binding 3.50e-03 6.91e-02 4.32e-01 4.22e-01 1.64e+00
go:0032432 actin filament bundle 3.59e-03 7.01e-02 4.32e-01 6.65e-01 1.83e+00
go:0120111 neuron projection cytoplasm 3.72e-03 7.11e-02 4.32e-01 5.87e-01 1.72e+00
go:0070849 response to epidermal growth factor 3.72e-03 7.11e-02 4.32e-01 6.63e-01 1.83e+00
go:0006415 translational termination 3.69e-03 7.11e-02 4.32e-01 -3.93e-01 -1.61e+00
go:0042326 negative regulation of phosphorylation 3.79e-03 7.12e-02 4.32e-01 3.82e-01 1.55e+00
go:0034728 nucleosome organization 3.81e-03 7.12e-02 4.32e-01 4.90e-01 1.71e+00
reactome:R-HSA-5689880 Ub-specific processing proteases 3.80e-03 7.12e-02 4.32e-01 -3.95e-01 -1.61e+00
go:0015980 energy derivation by oxidation of organic compounds 3.87e-03 7.16e-02 4.32e-01 -3.47e-01 -1.56e+00
go:0002703 regulation of leukocyte mediated immunity 4.10e-03 7.47e-02 4.07e-01 6.27e-01 1.80e+00
go:0032206 positive regulation of telomere maintenance 4.22e-03 7.60e-02 4.07e-01 5.81e-01 1.71e+00
go:0051054 positive regulation of DNA metabolic process 4.36e-03 7.60e-02 4.07e-01 4.89e-01 1.73e+00
go:0042026 protein refolding 4.31e-03 7.60e-02 4.07e-01 6.34e-01 1.78e+00
go:0005759 mitochondrial matrix 4.35e-03 7.60e-02 4.07e-01 -3.21e-01 -1.50e+00
go:0003724 RNA helicase activity 4.31e-03 7.60e-02 4.07e-01 6.26e-01 1.79e+00
go:0008094 DNA-dependent ATPase activity 4.54e-03 7.85e-02 4.07e-01 5.80e-01 1.78e+00
go:1902850 microtubule cytoskeleton organization involved in mitosis 4.57e-03 7.85e-02 4.07e-01 4.73e-01 1.71e+00
reactome:R-HSA-1226099 Signaling by FGFR in disease 4.64e-03 7.93e-02 4.07e-01 -5.83e-01 -1.83e+00
msig:M4013 KEGG_GAP_JUNCTION 4.73e-03 7.97e-02 4.07e-01 -6.53e-01 -1.86e+00
go:0099513 polymeric cytoskeletal fiber 4.72e-03 7.97e-02 4.07e-01 3.53e-01 1.51e+00
go:0016569 covalent chromatin modification 4.87e-03 8.14e-02 4.07e-01 3.74e-01 1.52e+00
go:0006974 cellular response to DNA damage stimulus 4.91e-03 8.16e-02 4.07e-01 3.14e-01 1.44e+00
go:0006954 inflammatory response 5.11e-03 8.26e-02 4.07e-01 -3.57e-01 -1.54e+00
reactome:R-HSA-445355 Smooth Muscle Contraction 5.09e-03 8.26e-02 4.07e-01 6.53e-01 1.80e+00
go:0009890 negative regulation of biosynthetic process 5.06e-03 8.26e-02 4.07e-01 2.96e-01 1.39e+00
reactome:R-HSA-6781823 Formation of TC-NER Pre-Incision Complex 5.07e-03 8.26e-02 4.07e-01 -5.49e-01 -1.84e+00
go:0005681 spliceosomal complex 5.15e-03 8.26e-02 4.07e-01 3.71e-01 1.52e+00
go:0044087 regulation of cellular component biogenesis 5.29e-03 8.45e-02 4.07e-01 3.20e-01 1.45e+00
go:0051240 positive regulation of multicellular organismal process 5.54e-03 8.71e-02 4.07e-01 2.97e-01 1.38e+00
go:0034399 nuclear periphery 5.57e-03 8.71e-02 4.07e-01 4.80e-01 1.68e+00
go:0005876 spindle microtubule 5.54e-03 8.71e-02 4.07e-01 5.87e-01 1.70e+00
go:0051130 positive regulation of cellular component organization 5.85e-03 9.08e-02 4.07e-01 2.97e-01 1.39e+00
go:1902115 regulation of organelle assembly 5.88e-03 9.08e-02 4.07e-01 4.60e-01 1.64e+00
reactome:R-HSA-8951664 Neddylation 6.08e-03 9.31e-02 4.07e-01 -3.76e-01 -1.57e+00
go:0005739 mitochondrion 6.11e-03 9.31e-02 4.07e-01 -2.40e-01 -1.29e+00
go:0071824 protein-DNA complex subunit organization 6.15e-03 9.32e-02 4.07e-01 3.98e-01 1.56e+00
go:0061061 muscle structure development 6.38e-03 9.61e-02 4.07e-01 3.83e-01 1.55e+00
reactome:R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 6.50e-03 9.63e-02 4.07e-01 -5.24e-01 -1.78e+00
go:0006338 chromatin remodeling 6.48e-03 9.63e-02 4.07e-01 4.44e-01 1.62e+00
go:0016491 oxidoreductase activity 6.79e-03 9.91e-02 4.07e-01 -2.89e-01 -1.41e+00
go:0030030 cell projection organization 6.83e-03 9.91e-02 4.07e-01 3.02e-01 1.40e+00
msig:M5945 HALLMARK_HEME_METABOLISM 6.92e-03 9.99e-02 4.07e-01 4.72e-01 1.65e+00

Literature Mining

INDRA was used to automatically assemble known mechanisms related to YOD1 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
YOD1 deubiquitinates VCP. 3 / 3
| 2

ubibrowser
The activity of the p97-associated deubiquitinylase YOD1 is also required for substrate disposal.

reach
P97 QQ associated polyubiquitinated proteins can be deubiquitinated in vitro by purified YOD1 (XREF_SUPPLEMENTARY).

reach
Ataxin-3 and YOD1 promote the deubiquitination of p97 associated ERAD substrates, and facilitate delivery to the proteasome [21-24].
YOD1 deubiquitinates ITCH. 3 / 3
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Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances the stability of ITCH, which leads to reduced levels of LATS and a subsequent increase in the YAP and TAZ level.

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Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances the stability of ITCH, which leads to reduced levels of LATS and a subsequent increase in the YAP and TAZ level.

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Deubiquitinase YOD1 potentiates YAP/TAZ activities through enhancing ITCH stability
YOD1 deubiquitinates DES. 2 / 2
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YOD1, a DUB from OTU family, deubiquitinates desmin.

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YOD1, a DUB from OTU family, deubiquitinates desmin.
YOD1 deubiquitinates SYVN1. 2 / 2
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In both of these scenarios, YOD1 would deubiquitinate Hrd1.

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If the cross-links represent Hrd1 oligomers, it is tempting to speculate that ubiquitination of Hrd1 favors its oligomerization; deubiquitination of Hrd1 by YOD1 would therefore prevent Hrd1 oligomerization.
YOD1 deubiquitinates NEDD4. 1 / 1
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YOD1 Deubiquitinates NEDD4 Involved in the Hippo Signaling Pathway.
YOD1-C160S leads to the deubiquitination of TRAF6. 1 / 1
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Also, catalytically inactive YOD1 C160S impaired the boost of TRAF6 auto-ubiquitination by p62, even though the inhibition was not quite as severe as with YOD1 WT.
YOD1 leads to the deubiquitination of CTA1. 1 / 1
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Because YOD1 knockdown did not promote CTA1 ubiquitination, despite increasing total cellular polyubiquitinated proteins, we propose that YOD1 imposes its negative role by deubiquitinating components of the ERAD machinery that normally promote retro translocation when ubiquitinated (XREF_FIG).
YOD1 deubiquitinates Gln-Gln. 1 / 1
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p97 QQ associated polyubiquitinated proteins can be deubiquitinated in vitro by purified YOD1 (XREF_SUPPLEMENTARY).

Other Statements

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
YOD1 affects NFkappaB
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YOD1 activates NFkappaB.
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YOD1 activates NFkappaB. 4 / 7
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However, why and how YOD1 promotes canonical NF-kappaB signaling and activation in the context of p62 independent CD40 or RANK stimulation is currently unclear and we can only speculate.

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Potentially, YOD1 could also function as a p97 co-factor for IkappaBalpha degradation to support canonical NF-kappaB signaling, but it is unclear why this would affect signaling in response to some inducers (e.g. CD40) while others are unaffected (e.g. IL-1 and TNF).

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Whereas knock-down of TRAF6 or p62 severely impaired IL-1beta triggered NF-kappaB activation as evident by EMSA, depletion of YOD1 enhanced NF-kappaB activation (XREF_FIG).

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YOD1 is released from TRAF6 upon IL-1 stimulation and YOD1 depletion enhances canonical NF-kappaB activation.
YOD1 inhibits NFkappaB.
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Further, IL-1 triggered IKK and NF-kappaB signaling and induction of target genes is decreased by YOD1 overexpression and augmented after YOD1 depletion.

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Using a transgenic mouse model, we confirmed that the Dox inducible expression of YOD1 in the liver enhanced the proliferation of hepatocytes, and led to hepatomegaly in a YAP and TAZ-activity-dependent manner.

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Targeting YOD1 by RNA Interference Inhibits Proliferation and Migration of Human Oral Keratinocytes through Transforming Growth Factor-

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Using a transgenic mouse model, we showed that the inducible expression of YOD1 enhances the proliferation of hepatocytes and leads to hepatomegaly in a YAP and TAZ-activity-dependent manner.

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Using a transgenic mouse model, we demonstrate that the inducible expression of YOD1 enhances the proliferation of hepatocytes and leads to hepatomegaly in a YAP and TAZ-activity-dependent manner.

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Interestingly, the inducible expression of YOD1 enhances the proliferation of hepatocytes and leads to hepatomegaly in a YAP and TAZ-activity-dependent manner.

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YOD1 RNAi may inhibit cell proliferation and migration associated with the pathogenesis of NSCL/P through TGF- beta 3 signaling.

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Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells.
YOD1 affects TRAF6
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YOD1 inhibits TRAF6. 4 / 6
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YOD1 antagonizes ubiquitin ligase TRAF6 and p62 dependent interleukin-1 signaling to NF-kappaB.

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We show that YOD1 competes with p62 for TRAF6 association and abolishes the sequestration of TRAF6 to cytosolic p62 aggregates by a non catalytic mechanism.

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Hence, our data define that YOD1 antagonizes TRAF6 and p62 dependent IL-1 signaling to NF-kappaB.

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Indeed, co-IP experiments using MYC-TRAF6 together with Crimson-p62 and GFP-YOD1 revealed that YOD1 was able to inhibit the association of TRAF6 and p62, while p62 did not alter the binding of YOD1 to TRAF6 (XREF_FIG).
MIR21 affects YOD1
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MIR21 inhibits YOD1.
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MIR21 inhibits YOD1. 4 / 4
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To further confirm that YOD1 inhibition and desmin downregulation is mediated by miR-21, we transfected cells with miR-362 as an additional non specific control, which showed no effect on the expression levels of gamma-catenin, desmin, YOD1 and ubiquitinated desmin.

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Similar reduction of YOD1 by miR-21 was observed in CVB3 infected samples (XREF_FIG).

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zTo confirm that the YOD1 suppression by miR-21 leads to the degradation of desmin during CVB3 infection, we utilized small interference RNA (siRNA) to knockdown endogenous YOD1, which mimicked the effect of miR-21 on YOD1 expression.

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Suppression of YOD1 by miR-21 promoted desmin degradation and desmosome disorganization.
MIR21 activates YOD1.
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MIR21 activates YOD1. 1 / 1
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Furthermore, infection by the enterovirus coxsackievirus B3 (CVB3) leads to cardiac failure by inducing miR-21 expression, which targets the deubiquitinating enzyme YOD1.
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Hsa-miR-98-5p decreases the amount of YOD1. 4 / 4
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Hsa-miR-1299 affects YOD1
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Hsa-miR-1299 decreases the amount of YOD1. 4 / 4
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YOD1 affects CTA1
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YOD1 inhibits CTA1.
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YOD1 inhibits CTA1. 1 / 1
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In contrast, the deubiquitinase YOD1 has been reported to negatively regulate CTA1 membrane extraction.
YOD1-C160S inhibits CTA1. 1 / 1
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To further dissect YOD1 's role in CTA1 retro translocation, we found that overexpression of the catalytically inactive C160S YOD1 but not WT YOD1 markedly decreased CTA1 arrival to the cytosol.
YOD1 decreases the amount of CTA1.
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YOD1 decreases the amount of CTA1. 1 / 1
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Using this semipermeabilized system, we found that YOD1 knockdown increased the CTA1 level in the supernatant fraction (XREF_FIG, top panel, compare lanes 2 and 3 with lane 1; quantified in XREF_FIG), suggesting that YOD1 normally exerts a negative function during ER-to-cytosol transport of the toxin.
YOD1 activates CTA1.
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YOD1 activates CTA1. 1 / 1
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Studies have shown that YOD1 negatively regulates the reverse transport of CTA1, and the mechanism of action may be the deubiquitination of some ERAD components that promote reverse transport of the protein rather than substrate ubiquitination.
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Hsa-miR-93-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-888-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-8073 affects YOD1
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Hsa-miR-8073 decreases the amount of YOD1. 3 / 3
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Hsa-miR-6839-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-6831-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-6818-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-661 affects YOD1
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Hsa-miR-661 decreases the amount of YOD1. 3 / 3
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Hsa-miR-583 affects YOD1
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Hsa-miR-583 decreases the amount of YOD1. 3 / 3
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Hsa-miR-5706 affects YOD1
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Hsa-miR-5706 decreases the amount of YOD1. 3 / 3
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Hsa-miR-5582-3p decreases the amount of YOD1. 3 / 3
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Hsa-miR-548o-3p decreases the amount of YOD1. 3 / 3
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Hsa-miR-516b-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-4782-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-4772-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-4764-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-4650-3p decreases the amount of YOD1. 3 / 3
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Hsa-miR-4500 affects YOD1
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Hsa-miR-4500 decreases the amount of YOD1. 3 / 3
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Hsa-miR-4458 affects YOD1
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Hsa-miR-4458 decreases the amount of YOD1. 3 / 3
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Hsa-miR-4316 affects YOD1
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Hsa-miR-4316 decreases the amount of YOD1. 3 / 3
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Hsa-miR-3927-3p decreases the amount of YOD1. 3 / 3
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Hsa-miR-383-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-378j affects YOD1
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Hsa-miR-378j decreases the amount of YOD1. 3 / 3
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Hsa-miR-3658 affects YOD1
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Hsa-miR-3658 decreases the amount of YOD1. 3 / 3
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Hsa-miR-3653-3p decreases the amount of YOD1. 3 / 3
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Hsa-miR-3614-3p decreases the amount of YOD1. 3 / 3
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Hsa-miR-3116 affects YOD1
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Hsa-miR-3116 decreases the amount of YOD1. 3 / 3
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Hsa-miR-221-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-2115-3p decreases the amount of YOD1. 3 / 3
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Hsa-miR-21-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-202-3p decreases the amount of YOD1. 3 / 3
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Hsa-miR-196b-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-196a-5p decreases the amount of YOD1. 3 / 3
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Hsa-miR-1323 affects YOD1
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Hsa-miR-1323 decreases the amount of YOD1. 3 / 3
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Hsa-miR-1294 affects YOD1
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Hsa-miR-1294 decreases the amount of YOD1. 3 / 3
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Hsa-miR-1254 affects YOD1
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Hsa-miR-1254 decreases the amount of YOD1. 3 / 3
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Hsa-miR-1237-3p decreases the amount of YOD1. 3 / 3
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Hsa-let-7i-5p decreases the amount of YOD1. 3 / 3
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Hsa-let-7g-5p decreases the amount of YOD1. 3 / 3
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Hsa-let-7f-5p decreases the amount of YOD1. 3 / 3
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Hsa-let-7e-5p decreases the amount of YOD1. 3 / 3
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Hsa-let-7d-5p decreases the amount of YOD1. 3 / 3
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Hsa-let-7c-5p decreases the amount of YOD1. 3 / 3
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Hsa-let-7b-5p decreases the amount of YOD1. 3 / 3
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Hsa-let-7a-5p decreases the amount of YOD1. 3 / 3
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YOD1 overexpression enhances cell migration by promoting TGF-beta3 signaling which may play an important role in lip and palate formation.

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RNA interference and overexpression experiments indicated that YOD1 could enhance cell migration during lip and palate formation through the transforming growth factor (TGF)-beta3 signaling pathway.

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RNA interference and overexpression experiments indicated that YOD1 could enhance cell migration during lip and palate formation through the transforming growth factor ( TGF ) - beta3 signaling pathway ( Zhou et al ., 2018 ) .
YOD1 affects SQSTM1
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YOD1 inhibits SQSTM1. 3 / 3
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Hence, our data define that YOD1 antagonizes TRAF6 and p62 dependent IL-1 signaling to NF-kappaB.

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YOD1 antagonizes ubiquitin ligase TRAF6 and p62 dependent interleukin-1 signaling to NF-kappaB.

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Indeed, co-IP experiments using MYC-TRAF6 together with Crimson-p62 and GFP-YOD1 revealed that YOD1 was able to inhibit the association of TRAF6 and p62, while p62 did not alter the binding of YOD1 to TRAF6 (XREF_FIG).
YOD1 affects IL1
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YOD1 inhibits IL1. 1 / 3
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Hence, our data define that YOD1 antagonizes TRAF6 and p62 dependent IL-1 signaling to NF-kappaB.
YOD1 affects MAVS
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YOD1 inhibits MAVS.
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YOD1 inhibits MAVS. 2 / 2
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The Otubain YOD1 Suppresses Aggregation and Activation of the Signaling Adaptor MAVS through Lys63 Linked Deubiquitination.

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Subsequently, YOD1 removes the K63 linked ubiquitin chain and abrogates the aggregation of MAVS, thus inhibiting not only IRF3 and p65 activation, but also IFN-beta production.
YOD1 activates MAVS.
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YOD1 activates MAVS. 1 / 1
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Liu and colleagues reported YOD1 mediated K63 linked deubiquitination could activate an innate antiviral immune response against viral infection, and the aggregation of MAVS.
YOD1 affects DES
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YOD1 activates DES.
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YOD1 activates DES. 2 / 2
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Suppression of YOD1 by miR-21 promoted desmin degradation and desmosome disorganization.

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Interestingly, both miR-21 and YOD1 siRNAs induced the re-distribution of desmin, resulting in increased co-localization of desmin and proteasomes.
YOD1 inhibits DES.
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YOD1 inhibits DES. 1 / 1
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Suppression of YOD1 Induces Desmin Degradation and Desmosome Disruption.
VCP affects YOD1
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VCP activates YOD1. 2 / 2
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VCP and p97 recruitment to lysosome membranes and functioning are mediated by its cofactors and adaptors YOD1, UBXD1, and PLAA.

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VCP and p97 recruitment to lysosome membranes and functioning are mediated by its cofactors and adaptors YOD1, UBXD1, and PLAA.
VCP bound to GEMIN4 activates YOD1. 1 / 1
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VCP and p97 recruitment to lysosome membranes and functioning are mediated by its cofactors and adaptors YOD1, UBXD1, and PLAA.
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Valproic acid decreases the amount of YOD1. 2 / 2
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Hsa-miR-7161-3p decreases the amount of YOD1. 2 / 2
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Hsa-miR-7-5p affects YOD1
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Hsa-miR-7-5p decreases the amount of YOD1. 2 / 2
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Hsa-miR-6806-3p decreases the amount of YOD1. 2 / 2
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Hsa-miR-643 affects YOD1
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Hsa-miR-643 decreases the amount of YOD1. 2 / 2
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Hsa-miR-6128 affects YOD1
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Hsa-miR-6128 decreases the amount of YOD1. 2 / 2
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Hsa-miR-6077 affects YOD1
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Hsa-miR-6077 decreases the amount of YOD1. 2 / 2
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Hsa-miR-6073 affects YOD1
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Hsa-miR-6073 decreases the amount of YOD1. 2 / 2
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Hsa-miR-520e affects YOD1
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Hsa-miR-520e decreases the amount of YOD1. 2 / 2
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Hsa-miR-520d-3p decreases the amount of YOD1. 2 / 2
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Hsa-miR-520c-3p decreases the amount of YOD1. 2 / 2
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Hsa-miR-520b affects YOD1
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Hsa-miR-520b decreases the amount of YOD1. 2 / 2
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Hsa-miR-520a-3p decreases the amount of YOD1. 2 / 2
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Hsa-miR-519d-3p decreases the amount of YOD1. 2 / 2
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Hsa-miR-3928-5p decreases the amount of YOD1. 2 / 2
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Hsa-miR-373-3p decreases the amount of YOD1. 2 / 2
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Hsa-miR-372-3p decreases the amount of YOD1. 2 / 2
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Hsa-miR-3606-5p decreases the amount of YOD1. 2 / 2
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Hsa-miR-3156-5p decreases the amount of YOD1. 2 / 2
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